Overview
UMB researchers have achieved significant clinical success with live vector vaccines based on attenuated Salmonella enterica serovar Typhi (proven safe in clinical trials). Adapting these typhoid vaccine strains for the delivery of foreign antigens offers exceptional flexibility for further vaccine development. Dr. Jim Galen's group devised multiple strategies to optimize such vaccines, including novel chromosal integration strategies (Ref. JG-2013-037), a non-antibiotic plasmid selection/stabilization system (Ref. JG-98-002) and protein export system (Ref. JG-2001-022 and JG-2008-080). These state-of-the-art strategies have been employed as the platform for an oral live vector vaccine against Clostridium difficile-associated disease. Synthetic genes for three important C. difficile virulence factors have been engineered for both genetic stability and efficient expression in an attenuated S. Typhi strain. The resulting live vector vaccine is currently being tested for its ability to elicit antigen-specific serum neutralizing antibodies and mucosal IgA response, and to protect against pathogen challenge in mice.
Applications
Clostridium difficile is a type of bacteria which can infect the human intestinal tract. It's harbored by 3% of healthy adults without symptoms but can cause disease ranging from mild diarrhea to more severe and life-threatening pseudomembranous colitis, which, if left untreated leads to fulminant colitis and death. Transmission of C. difficile occurs primarily in healthcare facilities via fecal to oral transmission from contaminated surfaces and hand contact. At risk for C. difficile-associated disease (CDAD) are the elderly and patients being treated with a prolonged course of antibiotics. In the U.S., data suggest mortality rates due to CDAD increased from 5.7 per million population in 1999 to 23.7 per million in 2004. Estimates of the cost for treatment in the U.S. have soared from $1 billion in 2002 to $3.2 billion in 2007, due to a dramatic increase in the number of cases and increasing severity of the disease. An emerging more virulent strain has been associated with recent epidemics of CDAD in North America and Europe, with increased morbidity and mortality.
Advantages
Broad humoral and mucosal immunity is anticipated with this vaccine, and that may not be readily achieved using another approach based on a purified protein subunit vaccine.
Stage of Development
UMB researchers have engineered the optimal multivalent, live vector C. difficile vaccine, and critical animal proof-of-concept experiments are underway.
R&D Required
Further pre-clinical development followed by clinical trials.
Licensing Potential
UMB seeks partner to advance this technology into the healthcare field.
Contact Info
Office of Technology Transfer
620 W Lexington St., 4th Floor
Baltimore, MD 21201
Email: [email protected]
Phone: (410) 706-2380